Variant 12-47667028-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024604.3(RPAP3):c.1864A>G(p.Lys622Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000169 in 1,536,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

RPAP3
NM_024604.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.89

Variant links:

Genes affected

RPAP3 (HGNC:26151): (RNA polymerase II associated protein 3) This gene encodes an RNA polymerase II-associated protein. The encoded protein may function in transcriptional regulation and may also regulate apoptosis. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

RPAP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39469945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RPAP3	NM_024604.3 linkuse as main transcript	c.1864A>G	p.Lys622Glu	missense_variant	16/17	ENST00000005386.8	NP_078880.2
RPAP3	NM_001146075.2 linkuse as main transcript	c.1762A>G	p.Lys588Glu	missense_variant	15/16		NP_001139547.1
RPAP3	NM_001146076.2 linkuse as main transcript	c.1387A>G	p.Lys463Glu	missense_variant	15/16		NP_001139548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPAP3	ENST00000005386.8 linkuse as main transcript	c.1864A>G	p.Lys622Glu	missense_variant	16/17	2	NM_024604.3	ENSP00000005386	P1	Q9H6T3-1
RPAP3	ENST00000380650.4 linkuse as main transcript	c.1762A>G	p.Lys588Glu	missense_variant	15/16	1		ENSP00000370024		Q9H6T3-2
RPAP3	ENST00000432584.7 linkuse as main transcript	c.1387A>G	p.Lys463Glu	missense_variant	15/16	2		ENSP00000401823		Q9H6T3-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000104

AC:

AN:

192066

Hom.:

AF XY:

0.00000944

AC XY:

AN XY:

105956

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000210

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1384426

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

688000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000194

Gnomad4 OTH exome

AF:

0.0000525

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2023

The c.1864A>G (p.K622E) alteration is located in exon 16 (coding exon 15) of the RPAP3 gene. This alteration results from a A to G substitution at nucleotide position 1864, causing the lysine (K) at amino acid position 622 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

T;.;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

T;T;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

0.86

N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.029

D;D;D

Polyphen

0.78

P;.;P

Vest4

0.39

MutPred

0.46

Loss of ubiquitination at K622 (P = 0.0218);.;.;

MVP

0.43

MPC

0.44

ClinPred

0.64

GERP RS

4.5

Varity_R

0.55

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over